Exertional exhaustion is the critical aspect that distinguishes myalgic encephalomyelitis/CFS from other nociceptive, interoceptive, and fatiguing illnesses.

The lack of energy may be caused by autoimmune and metabolomic dysfunction that reduces mitochondrial ATP production.

The primary goals of management are to provide a supportive healthcare environment with a team of occupational, physio, and other appropriate therapists who will manage symptoms and improve functional capacity.

The chronic but fluctuating disabilities require substantial lifestyle changes to plan each day's activities carefully, conserve energy resources for the most important tasks, schedule rest periods to avoid individuals overtaxing themselves, and to improve the quality of sleep.

Medications are not curative. Pharmacotherapy is indicated to treat pain, migraine, sleep disturbance, and comorbid conditions such as irritable bowel syndrome, anxiety, or depression.

Exertional exhaustion is the critical aspect that distinguishes ME/CFS from other nociceptive, interoceptive, and fatiguing illnesses. This means people with CFS must make significant lifestyle changes to conserve their physical resources and mental concentration to stay competent in normal occupational, educational, and social settings. They are often limited to a few hours per day of productive endeavours, with the remainder of the time spent resting with slow and partial recovery from the disorganised thoughts, total body pain, malaise, and other features of their chronic fatigue state. Consideration of 'fatigue' as mental or physical tiredness is too simplistic to encompass the scope of impairment in CFS, and belies the inadequacy of the vocabulary of fatigue. There is a strong bias to the vocabulary of acute viral illness, such as influenza and poliomyelitis, because these were considered historical precedents of CFS.

CFS is characterised by a sudden or gradual onset of persistent disabling fatigue, post-exertional malaise (PEM, exertional exhaustion), unrefreshing sleep, cognitive and autonomic dysfunction, myalgia, arthralgia, headaches, and sore throat and lymph nodes, with symptoms lasting at least 6 months.
[8]Komaroff AL. Myalgic encephalomyelitis/chronic fatigue syndrome: a real illness. Ann Intern Med. 2015;162:871-872.
http://annals.org/article.aspx?articleid=2322808
http://www.ncbi.nlm.nih.gov/pubmed/26075760?tool=bestpractice.com
PEM is the hallmark of CFS. The fatigue is not related to other medical conditions, and symptoms do not improve with sleep or rest.

Systemic exertion intolerance disease (SEID) was defined by the US Institute of Medicine (IOM). Diagnosis of SEID requires disabling fatigue, PEM, unrefreshing sleep, and cognitive and autonomic dysfunction that is persisting, moderate or severe, and present at least 50% of the time in order to denote the unique symptom spectrum.
[4]Institute of Medicine of the National Academies. Beyond myalgic encephalomyelitis/chronic fatigue syndrome: redefining an illness. February 2015. http://iom.nationalacademies.org (last accessed 30 May 2017).
http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFS_ReportBrief.pdf

It is inappropriate to use the 1991 Oxford criteria of fatigue as an alternative for CFS because the Oxford criteria are based on 'mild fatigue', do not require PEM, and allow inclusion of chronic idiopathic fatigue, depression, and other fatiguing conditions.
[9]Sharpe MC, Archard LC, Banatvala JE, et al. A report - chronic fatigue syndrome: guidelines for research. J R Soc Med. 1991;84:118-121.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293107/
http://www.ncbi.nlm.nih.gov/pubmed/1999813?tool=bestpractice.com
Up to 30.5% of the population have chronic fatigue
[10]van't Leven M, Zielhuis GA, van der Meer JW, et al. Fatigue and chronic fatigue syndrome-like complaints in the general population. Eur J Public Health. 2010;20:251-257.
http://www.ncbi.nlm.nih.gov/pubmed/19689970?tool=bestpractice.com
and would meet Oxford criteria for study inclusion. Studies that used the Oxford criteria are not representative of the more severe and restricted definitions of CFS that the CDC, Canadian Consensus, or SEID criteria define. Exercise and cognitive behavioural therapy studies that used the Oxford criteria for study inclusion are biased and misleading because people with true CFS are underrepresented, with excessive recruitment of people with chronic idiopathic fatigue and depression who are known to respond well to these modalities.
[11]Geraghty KJ. 'PACE-Gate': When clinical trial evidence meets open data access. J Health Psychol. 2016 Nov 1 [Epub ahead of print].
http://www.ncbi.nlm.nih.gov/pubmed/27807258?tool=bestpractice.com

Disclosures

Dr James N. Baraniuk would like to gratefully acknowledge Dr Craig N. Sawchuk and Dr Dedra Buchwald, the previous contributors to this monograph. CNS declares that he has no competing interests. DB is an author of a number of references cited in this monograph.